Significance HIV is a sexually transmitted disease and a vaccine capable of preventing sexual transmission of HIV should elicit mucosal immune responses in the genital tract. This study should determine if immunzation at distant mucosal sites can result in protection from vaginal HIV exposure. Objective SHIV89.6 is a chimeric virus which includes the regulatory and envelope genes of HIV-1 89.6 and the polymerase and core proteins of SIVmac239. This virus infects rhesus macaques but does not cause disease and can be a considered an attenuated vaccine. We have shown that intravaginal inoculation of SHIV 89.6 can protect animals from subsequent vaginal challenge with virulent SIVmac239. It is not known if it necessary to specific stimulate the immune system in the vaginal mucosa to achieve this protetcion. To test the hypothesis that vaginal protection can be achieved by stimulating distant mucosal immune sites which results in vaginal immune responses, we have intranasally immunized 3 rhesus macaques with SHIV 89.6 mixed with cholera toxin and 3 rhesus macaques with SHIV 89.6 alone. The animals were inoculated 3 times over the course of a week. Results All 6 animals became infected by intranasal immunization. We are in the process of characterizing the immune responses in these animals and, they will be challenged by intravaginal inoculation of virulent SIVmac shortly. Future Directions Complete challenge study, then if indicated pursue other routes of eliciting protection from vaginal SIV infection. KEYWORDS SHIV vaccine, mucosal immunity, intranasal immunization, SIV vaginal transmission